Device for Performing a Chemical Transformation in Fluidic Media

ABSTRACT

A device is provided for performing chemical transformation in a fluid, with a flow distributor having at least one fluid medium inlet, at least one fluid medium outlet, and at least one confinement wherein the chemical transformation is performed; and a means for rotating, rocking, wagging, or oscillating the device. At least one confinement may be equipped with a provision for providing heat, cooling, sound, light or other types of radiation, such provision being contacted to an external source through an actuator shaft. The flow distributor may be provided with sectors connected with the centrally located fluid medium inlet and a designated peripheral, fluid medium outlet. The means for rotating, rocking, wagging, or oscillating the device may be an element producing magnetic fields or a shall mechanically connected to an external actuating device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. provisional application Ser.No. 61/337,915 filed Feb. 12, 2010.

FIELD OF THE INVENTION

The present invention relates to devices for performing biological orchemical transformation, or physical or chemical trapping, comprising ofone or more confinements, wherein a desirable fluidic flow through theconfinement(s) is created by rotating, rocking, wagging, or oscillatingthe device.

BACKGROUND OF THE INVENTION

Heterogeneous processes in chemistry and biotechnology encompassing asolid member (including, but not limited to, immobilized chemicalreagent, catalyst, scavenger, reaction support, or trapping sorbent, orimmobilized biological, materials such as cells or fragments thereof)contacting a fluidic medium carrying reactants or other agents, samplesolutes, and/or products of the interactive processing of fluid-conveyedagent(s) with the solid member(s) are critically dependent on convectiveflow to accomplish the necessary mass transfer between the two phases.Such systems are therefore often operated in a continuous flow throughmode, in which case a conventional packed column with a suitable designis often the preferred format for encapsulating the solid member that isto be transited or percolated by the reaction medium. Numerous processesare, however, unfit for continuous processing. This applies inparticular to processes where sequential addition of agents and/orremoval of by-products or desired products are necessary, or where thephysical or chemical conditions must otherwise be altered during thecourse of processing with the solid, member, in those cases a batch-wiseprocessing mode is often preferred. Such batch-wise heterogeneousprocessing can either be done by suspending the solid member directly inthe fluidic medium as particulate material under agitation, a processthat will normally call for a filtration or sedimentation step toseparate the phases after the process has been brought to an end.Alternatively, the fluidic medium can be circulated from the batchreactor through a packed reservoir containing the solid member by meansof a specially designed flow system comprising pumps and/or valves orthe like, in order to accomplish the convective mass transfer needed forthe reactions to take place. Such reactors are often quite complicatedand must regularly be built for the specific purpose.

The challenge of establishing efficient convective mass transfer betweensolid and fluidic phases has been addressed, e.g., by applying the solidmember as a coating on the external surface of a rotating device (E.Baltussen, et al., J. Microcolumn Separations, 11 (1999) 737-747; U.S.Pat. No. 6,815,216), as well as on the inside of narrow tubes coatedwith solid member through which the fluidic medium is conveyed byconventional pumping R. Eisert, J. Pawliszyn, Anal. Chem., 69 (1997)3140-3147; U.S. Pat. No. 5,691,206). While these products may be fit forthe analytical sampling purposes for which they were designed, theamount of solid member that can be incorporated will be severely limitedin systems where only the external or internal surface has been modifiedto act as the solid member. Further, since the surface area does notincrease linearly with the volume of a reactor where the solid member isdeposited on the surfaces only, such systems are also not well suitedfor up-scaling.

U.S. patent application publication no. 2007/0189115 discloses a hollowmagnetic stirrer designed to create an internal flow when rotated. Thestirrer is not designed to house any solids for performing biological orchemical transformation, or physical or chemical trapping.

U.S. Pat. No. 6,857,774 B2, representing the closest prior art,discloses a device for cavitational mixing and pumping. This performanceof the device described in this piece of prior art is partially based onthe same principles as the device of the present invention, i.e., thegeneration of a flow using a centripetal force field. However, thedevices according to U.S. Pat. No. 6,857,774 B2 do not comprise aconfinement which can house a solid member for carrying out thetransformation and/or trapping actions that are the scope of theinvention disclosed here, and the purpose of the devices described inthe prior art is fundamentally different, namely to promote cavitationto establish sonochemical reaction conditions in homogeneous solution.

SUMMARY OF THE INVENTION

The present invention deals with a general principle for the design ofdevices suitable for batch or continuous mode heterogeneous processingin vessels of varying, size, and encompasses an entity containing one ormore solid member(s) in internal confinement(s), through which thechallenge of creating a convective flow of fluidic medium through theinternally contained solid member is established simply by rotating,rocking, wagging, or oscillating the device when it is immersed in thefluidic medium. Since the solid member is contained in internalconfinement(s), the volume of the solid member will scale linearly withthe overall reactor volume, hence providing for a substantially betterscalability compared to active rotating sampling devices known fromprior art (E. Baltussen, et al., J. Microcolumn Separations, 11 (1999)737-747; U.S. Pat. No. 6,815,216), where the solid member is coated onthe surface only. The present invention also offers considerable designadvantages through the confinement of the solid member inside thedevice, which effectively eliminates problems inherent in a device witha non-contained solid member, such as clogging of vents and filters,caused by wear of the coatings that are deposited on the outer surface.

Accordingly, the present invention provides a device for performingbiological or chemical transformation, or physical or chemical trappingin fluidic media comprising:

a flow distributor having at least one fluid medium inlet, at least onefluid medium outlet, and at least one confinement connected to theinlet(s) and outlet(s) wherein the transformation or trapping isperformed; and

a means for rotating, rocking, wagging, or oscillating the device.

The confinement(s) are spatially arranged within the device so that thecentrifugal force, a flow-induced pressure differential, and/or aninertial force are established by rotating, rocking, wagging, oroscillating the device, thereby forcing the fluidic medium in which thedevice is submerged to flow through the confinement(s) of the flowdistributor.

Preferably the flow distributor has one or more central fluid mediuminlet(s).

Preferably the flow distributor has one or more peripheral fluid mediumoutlet(s).

Preferably the confinement(s) of the flow distributor houses one or moresolid members that participates in or facilitates a biological orchemical transformation involving at least one agent distributed withthe flow, alternatively causing the agent to become trapped by a solidmember.

The terms “chemical transformation” and “chemical reaction” are usedinterchangeable herein and are intended to include both chemical andbiological transformations, as well as chemical and physical trapping.

According to one embodiment of the invention the confinement ispositioned symmetrically to the central axis of the flow distributor.

According to another embodiment of the invention the one or moreconfinements are peripherally located in the flow distributor.

According to one embodiment of the invention the flow distributor hasone fluid medium inlet and one or more fluid medium outlet(s) located ina plane above the plane of the fluid medium inlet.

According to one preferred embodiment of the invention the flowdistributor has a confinement located so that a fluid medium flowsthrough the confinement before it diverges to the fluid outlets.

According to another embodiment of the invention the flow distributorhas confinement laid out as a spiral-formed flow channel from thecentral fluid medium inlet to the peripheral outlet.

According to one embodiment of the invention the flow distributor ismade from or coated with a material that is able to catalyze at leastone agent to undergo a chemical reaction.

According to another embodiment of the invention the flow distributorhas the solid member incorporated as a coating that is capable ofchemically transforming at least one agent introduced to the flowchannel.

According to yet another embodiment of the invention the flowdistributor is circular or eliptic in cross-section and provided with aplurality of sectors, each sector being connected with the centrallylocated fluid medium inlet and a designated peripheral fluid mediumoutlet

Preferably the flow distributor has an outer or peripheral stationarypart provided with a plurality of sectors and an inner central part thatis adapted to rotate with the means for agitation.

Preferably the sectors are provided, with the same or different solidmembers, which are made from a material that is capable of biologicallyor chemically transforming, or trapping at least one agent introduced tothe sectors.

According to one embodiment of the invention the means for rotating,rocking, wagging, or oscillating the device is a magnet driven by afluctuating external magnetic field.

According to another embodiment of the invention the means for rotating,rocking, wagging, or oscillating the device is a solid or hollow shaftmechanically connected to an external actuating device.

Preferably at least one confinement is further equipped with means forproviding exchange of matter or energy such as addition of reagents orremoval of products and by products, heating or cooling, or applicationof acoustic energy, ultraviolet or visible light or other types ofelectromagnetic radiation, the provision for exchange of matter orenergy being contacted to an external source through the actuator shaft.

Preferably the provision for exchange of electromagnetic energy is usedto provide microwave radiation, ultraviolet or visible light, and/oracoustic energy to assist reactions taking place in the flowdistributor.

Preferably the provision for exchange of mailer is used to provide a gasthat can react with at least one agent in the fluidic medium, and/orwith at least one agent that is located in the flow distributor, the gasbeing provided through the actuator shaft.

According to one embodiment of the invention the confinement contains asolid member which is a catalyst.

According to another embodiment of the invention the confinementcontains a solid member containing a physically trapped or chemicallybonded reagent capable of entering chemical reaction with an agenttransported by the fluidic flow.

According to yet another embodiment of the invention the confinementcontains a solid member which is an immobilized biological entitycapable of transforming agents supplied by the fluidic flow.

According to yet another embodiment of the invention the confinementcontains a solid member which is a support material suitable forcarrying out solid phase synthesis.

According to yet another embodiment of the invention the confinementcontains a solid member which is a solid sorbent capable of trappingmatter from the fluidic flow.

According to yet another embodiment of the invention the confinementcontains a solid, member which is a stationary phase suitable forchromatographic separation.

According to one preferred embodiment of the invention two or moreconfinements are connected in series, and are filled with differentsolid members.

According to another preferred embodiment of the invention two or moreconfinements are connected in parallel and are filled with differentsolid members.

Preferably the device according to the present invention comprisescombination of confinements connected in series and parallel.

Preferably the solid member(s) are provided in one or more cartridgeswhich are placed within the confinements). Preferably the cartridges arereplaceable for ease of operation.

According to another embodiment of the invention the internal channelsof the flow distributor have been laid out so that an internal flow isestablished mainly by inertial action.

According to another embodiment of the invention the device furthercomprises at flow-operated valve located between the inlet(s) to theoutlet(s) of the flow distributor, where rocking the device or rotationof the device by alternating rotating speed causes liquid to flow fromthe inlet, to the outlet.

Another aspect of the present invention provides at method forperforming biological or chemical transformation, or physical orchemical trapping in fluidic media, said method comprising creating aconvective flow of fluidic medium through a device by rotating, rocking,wagging, or oscillating the device, where said device comprises a flowdistributor having at least one fluid medium inlet, at least one fluidmedium outlet, and at least one confinement connected to said inlet(s)and outlet(s) wherein said transformation or trapping is performed.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a drawing outlining an example of a device according to theinvention in its simplest form, actuated by a shaft and incorporating asolid member.

FIG. 2A shows a solid and FIG. 28 shows a cross-sectional view of amagnetically actuated tubular device of the invention constructedaccording to the general principles of the invention, based on thecentrifugal force and possibly also the Bernoulli effect.

FIG. 3 illustrates how two pairs of identically shaped solid members Aand B, carrying different functionalities, can be incorporated in serialand parallel fashion. FIG. 3A shows an empty device, FIG. 3B shows adevice where solid member A is incorporated in a single configuration.FIG. 3C a device where solid member a and B are incorporated in a serialconfiguration. FIG. 3D shows a device where solid members A and B areincorporated, in a parallel configuration.

FIG. 4 shows a device of the invention formed as a hollow puck-shapedwhere a conventional solid magnetic spin bar is used both for actuationand for dividing the interior space into two separate compartments.

FIG. 5 shows a device of die invention formed as a hollow puck withfixed sectors, that can be adapted either for mechanically ormagnetically coupled actuation.

FIG. 6 shows a device of the invention and designed as a hollow puckwith exchangeable inserts.

FIGS. 7A and 7B show a mechanically actuated device of the inventiondesigned to operate predominantly according to the Bernoulli principle.FIG. 7A shows a side view of the device. FIG. 7B shows a top view of thedevice.

FIG. 8 shows a device of the invention constructed with a rotating innerpart and a static outer part designed to minimize vortex formation.

FIGS. 9A-9D show a device of the invention based mainly on the principleof inertia, with peripherally arranged fluid outlets. FIG. 9A shows atop view of the device in the plane A-A indicated in FIG. 9C. FIG. 9Bshows a top view of the device in the plane B-B indicated in FIG. 9D,FIG. 9C shows a side view of the device in the plane C-C indicated inFIG. 9A, FIG. 9D shows a side view of the device in the plane D-Dindicated in FIG. 9A.

FIGS. 10A-10D show a device of the invention based mainly on theprinciple of inertia, with a centrally arranged fluid outlet, suitablefor stacking. FIG. 10A shows a top view of the device in the plane E-Findicated in FIG. 10C. FIG. 10B shows a top view of the device in theplane F-F indicated in FIG. 10D. FIG. 10C shows a side view of thedevice in the plane G-G indicated in FIG. 10A, FIG. 10D shows a sideview of the device in the plane indicated in FIG. 10A.

FIGS. 11A-11D show a device of the invention based mainly on theprinciple of inertia, with internal flow channels routed as multipleparallel archimedean spirals. FIG. 11A shows a top view of the device inthe plane I-I, indicated in FIG. 11D. FIG. 11B shows a top view of thedevice in the plane indicated in FIG. 11C. FIG. 11C shows a side view ofthe device in the plane K-K indicated in FIG. 11A. FIG. 11D shows a sideview of the device in the indicated in FIG. 11A.

FIGS. 12A-12D show a device of the invention based mainly on theprinciple of inertia, with internal how channels routed as multipleparallel archimedean spirals and where the outlet is routed back to thecentral axis. FIG. 12A shows a top view of the device in the plane M-Mindicated in FIG. 12D. FIG. 12B shows a top view of the device in theplane N-N indicated in FIG. 12C. FIG. 12C shows a side view of thedevice in the plane O-O indicated in FIG. 12A. FIG. 10D shows a sideview of the device in the plane P-P indicated in FIG. 12A.

DETAILED DESCRIPTION OF THE INVENTION

The present invention utilizes a limited number of fundamental physicalprinciples to facilitate the design of a closely related and novel setof devices. The devices according to the present invention, all based onthe same set of basic principles, can be utilized to perform biologicalprocesses, chemical reactions, or physical or chemical trapping withinits confinement(s) when operated in vessels of varying dimensions. Ingeneral terms, the present invention relates to a device comprising aflow distributor, having its internal plumbing laid out purposely withat least one fluid medium inlet, at least one fluid outlet, and at leastone confinement, combined with a means for agitation of the device byrotating, rocking, wagging, or oscillation (henceforth referred to as“applicable agitation modes”) so that either the fictitious centrifugalforce related to the rotating reference frame (referred to shorter as“centrifugal force” onwards), the Bernoulli principle acting through thepressure decrease caused by fluidic flow, mainly past the peripheralexits, and/or inertia produced by a rocking, wagging, or oscillatingmotion, singly or combined, provides the driving force(s) forestablishing a flow of fluid medium from the fluid inlet(s) to the fluidoutlet(s) through the flow distributor and the confinement(s) of theflow distributor when the device is immersed in the fluidic medium andagitated in an agitation mode applicable for that particular devicedesign variant. The reason why several fundamentally different physicalprinciples are mentioned as being active in establishing an internalfluidic flow in the device, is that more than one of these may be ineffect at any given time in a device that has been constructed andoperated according to the general principle disclosed here. It will, inthat, be difficult to produce a functional device according to thegeneral principle in which at least the centrifugal force and theBernoulli principle would lack any significance for establishing a flowof fluidic medium through the device when operated by steady,non-oscillating actuation, as disclosed inmost of the design examplesbelow. The flow distributor so constructed is adapted to allow at leastone agent that is conveyed by the fluidic flow, or provided to the flowdistributor by other means, to undergo a biological process or achemical reaction, and/or become physically or chemically trapped. Suchprocessing, reaction, and/or trapping taking place in the confinement(s)of the flow distributor may be accomplished on, or promoted by,interactions with (a) solid reaction member(s) deposited inside theconfinement of the flow distributor as a space-filling particulate ormonolithic packing, or on its inner surfaces only, and/or by directinginto the confinement of the flow distributor electromagnetic radiationsuch as (but, not limited to) ultraviolet light or microwaves, oracoustic energy, through a mechanical actuator element. The inventiondoes not include use of a simple solid member packed in or coated on theinside walls of a container per se, a practice that is well known inmany areas of prior art; the inventive moment communicated herein isinstead the combination of a device which by itself and due to thelayout of its inlet(s), internal channeling, and outlet(s) is capable ofestablishing an internal flow of fluidic medium when being actuated inone or more of the above the applicable agitation modes, with one ormore solid reaction or trapping member(s) contained internally in thedevice.

Products resulting from reaction(s) taking place inside the device couldeither be transported out through the outlet(s), or allowed toaccumulate on a solid reaction member, for instance in the widely usedheterogeneous reaction schemes based an immobilized cells inbiotechnology and solid, phase synthesis in chemistry. Furthermore, inseveral of the embodiments described below, devices manufacturedaccording to the disclosed principle can be designed to accommodate morethan one solid reaction member, either mixed in a single confinement, orspatially separated in more than one internal confinement, where theconfinements containing separated members could be connected either inseries or in parallel, or any combination thereof. It would thereby bepossible to use any combination of immobilized biomaterials, chemicalreagent carriers, reaction supports or catalysts, chromatographicseparation media, or trapping sorbents simultaneously in the samedevice. A particularly valuable envisioned use of a multi-confinementdevice would be biological or chemical conversion combined with in-linetrapping, or sequential reactions with two or more reagents that areantagonistic unless immobilized on solid carriers, the latter welldescribed in prior art (C. V. Pittman, L. R. Smith, J. Am. Chem. Soc.1975, 97, 1749-54. B. J. Cohen, M. A. Kraus, A. Patchornik, J. Am. Chem.Soc. 1977, 99, 4165-7; B. J. Cohen, M. A. Kraus, A. Patchornik, J. Am.Chem. Soc. 1981, 103, 7620-9; T. H. Maugh, Science, 1982, 217, 719-20).A batch-mode bioreactor prone to product down-regulation, or a catalyzedchemical reaction where the catalyst is poisoned by the product(s) arealso fully feasible examples of devices according to the invention within-line trapping of produced material using the technique describedhere.

The shape of the device could be cylindrical, spherical, cubical, or anyother shape through which it possible to establish an internal fluidtransport effected by a pressure differential, by centrifugal force,and/or by inertia, forces established solely by rotating, rocking,wagging, or oscillating the device itself.

In one embodiment of the invention, the device is rotated at a constantor varying angular velocity, and comprises at least one confinementsuitable for carrying out biological or chemical reactions, or physicalor chemical trapping. The confinement(s) to be transited or percolatedby a fluid medium flow is(are) preferably positioned symmetrical to therotational axis of the flow distributor, so that the fluid medium flowsthrough the confinement(s) before it diverges into the fluid outlet(s).Alternatively, one of more confinement(s) is(are) located peripherallyin the flow distributor, where they are transited or percolated by aflow of fluidic medium that has been manifolded from a single fluidmedium inlet, in case a plurality of confinements is used. Preferably,accordion to the embodiment, the flow distributor has one fluid mediuminlet located near or at the momentum axis and two or more fluid mediumoutlets located close to the perimeter of a circle described by thedevice then agitated around the central axis or its center of mass.Preferably the flow distributor of the device according to the inventioncomprises one or more confinements that could either be empty or filledwith a solid member. The solid member housed by these confinements cancomprise immobilized biologically active materials such as cells orfragments thereof, a catalyst capable of promoting a chemical reaction,a stationary phase that can carry out separations according to theprinciples of chromatography, a sorbent that can effectuate selectivetrapping of one or more agents transported by the fluidic flow, a porousor non-porous solid reagent carrier, or a porous or non-porous solidreaction support, where the reagent carrier or reaction support maycontain covalently or non-covalently bonded reagent(s), trappedliquid(s) or gas(es), or any other material that can react with at leastone anent comprised in the fluidic medium, or, through the henceestablished fluid transport, with one or more agents that is/are locatedin the flow distributor. In a preferred alternative of this embodiment,the reaction confinement is located centrally in the flow distributorand meets a medium flow from a central inlet of the flow distributorwhich is provided with two or more peripheral exits.

In yet another embodiment of the device, the flow distributor iscircular or elliptic in cross-section and provided with a plurality ofconfined sectors, with each sector connected with the centrally locatedfluid medium inlet and a designated peripheral fluid medium outlet. Thecompartments thus sectorized can optionally be left empty, have theirsurfaces coated by, or be tilled with, identical or different solidmember(s) made from fluid-permeable material(s) that is/are capable ofeither trapping, or entering into a biological or chemicaltransformations of, at least one agent introduced to the sectors by thefluid medium, or provided to the sectors in alternative ways. In oneadvantageous alternative, the flow distributor has a non-rotating outer(peripheral) stationary part provided with a plurality of sectors, andan inner central part that is adapted with a means for rotation.Advantageously, as with the inertial device described below, such adesign with a rotating core element and a static peripheral elementcounteracts the tendency of the bulk fluid medium to move with the meansfor rotation, which supports the efficacy of the device as a reactor bysupporting a high internal flow from the central inlet to the outletslocated at the periphery of the device without resulting in formation ofa rotational vortex.

In the so described embodiments, the means for rotating, rocking,wagging, or oscillating the device are well described in prior art, andcan either be a direct mechanical connection to an external actuator, orindirect coupling to an external force field, notably, but not limitedto, the coupling of a ferromagnetic element contained in the device to afluctuating external magnetic field, the fluctuating field beingestablished either by properly positioning in the vicinity of the devicea ferromagnetic or electromagnetic field source actuated by mechanicalmeans, or a plurality of stationary electromagnets that are actuated byan electronic circuit in the proper sequence required for thatparticular agitation mode (in its essence constructed according to theprior art principles disclosed by Zipperer (U.S. Pat. No. 3,554,407))which effectively converts the device into the rotor of an electricmotor through its internal ferromagnetic element. A particular advantagewith the electromagnetic coupling scheme is that all forms of agitationdisclosed as possible for establishing an internal fluid flow throughthe flow distributor in this invention (rotating, rocking, wagging, oroscillation) can be implemented by purely electromagnetic means withoutthe need for moving parts, by properly positioning and sequentiallyactuating the electromagnets in a variety of spatial configurations.Means for rotating, rocking, wagging, or oscillating the device based onthe electromagnetic coupling principle are furthermore advantageous whenan explosion risk is at hand, as well as in sealed reactors wheremechanical shafts impose a leakage problem.

The flow distributor can optionally be filled with a fluid-permeablematerial that is capable of catalyzing at least one agent in the fluidicmedium to undergo a chemical reaction. In another alternative, thechannel is shaped into a spiral which surface is coated with a materialthat is capable of chemically transforming at least one agent introducedto the flow channel. When combined with a check valve in the centralinlet such a spirally shaped confinement fulfills the channelorientation criteria for an inertial device, as outlined in the belowpreferred embodiment.

In the described embodiments, a flow distributor that is directlyconnected to a mechanical actuator can further be equipped through theactuator coupling with a means for providing exchange of matter orenergy, such as addition of reagent and/or removal of products orby-products, heating or cooling, introduction of acoustic energy, orapplication of electromagnetic radiation such as an integrated sourceof, or a waveguide for, light of different wavelengths (ultraviolet,visible, or infrared), or microwave radiation, designed to be connectedwith one or more reaction confinement(s) of the flow distributor. Theprovision for exchange of matter or energy hence established isgenerally contemplated to provide a suitable set of physical conditionsfor bringing about a specific desired biological or chemical reaction,or to control, accelerate, or delay a biological or chemical reaction.In one alternative, the provision for exchange of matter or energy ispreferably connected to an external source through the actuator shaft.Introduction of such a device into a reaction vessel can create a localreactor inside the vessel, with means for exchange of above the matteror energy, as well as for transmission of signals from any sensor thatmay be positioned within the flow distributor, through the actuatorshaft.

Devices constructed according to the disclosed general principle areapplicable with a variety of biological or chemical reactions orprocesses, including, but not limited to cell culture, biocatalysis,enzyme engineering, ion exchange processes, selective removal by solidsupported, scavengers, catalysis with heterogeneous catalysts, Grignardreactions or any form of metal reagents, linkers, oligonucleotide orpeptide synthesis, and organic synthesis.

What has been outlined in general terms are the important features ofthe invention in order that the detailed description thereof may bebetter understood, and in order that the present contribution to the anmay be better appreciated. Additional features of the invention will bedescribed hereinafter in the detailed description of invention.

In this respect, before explaining at least one embodiment of theinvention in detail, it is to be understood that the invention is notlimited in its application to the details of construction and to thearrangements of the components set forth in the following description orillustrated in the drawings. The invention is capable of otherembodiments and of being practiced and carried, out in various ways.Also, it is to be understood that the phraseology and terminologyemployed herein are for the purpose of the description and should not beregarded as limiting.

Once the general principle has been validated, a variety of devicedesigns can be envisioned to fulfill the general principles ofoperation, as outlined in the preceding pans of this disclosure. Asummary of example designs follows. It should be understood that theseserve as examples only of the general principle of establishing internalflow through a reactor device by its movement. The scope of theinvention shall thus not be limited designs made according to theseexamples.

In the embodiment depicted in FIG. 1, the chemical reactor device is agenerally hollow tubular entity rotated in a fluid medium by mechanicalforce through a shaft, that can also act as an integrated means forproviding exchange of matter or energy. Arrows in FIG. 1 indicate fluidflow (dotted line) and rotation (solid line), respectively. The devicehas flow distributor (11) which in cross-sectional view is generallyT-shaped. A fluid inlet (12) is axially located, and so is the reactionconfinement (13), towards which the actuation shaft (14) is extended. Inthis embodiment the actuation shaft (14) is the means for rotating,rocking, wagging, or oscillating the device. This shaft can be hollow toallow incorporate means for transferring ancillary reactants, productsor by-products, heat, acoustic energy, or electromagnetic radiation suchas (but not limited to) ultraviolet light or microwaves. When such adevice is rotated, a pressure differential is established from the axialinlet (12) to the peripherally located outlets (15) due to the Bernoullieffect acting on outlet orifices. This pressure differential isaugmented by the centrifugal force, which assists in forcing the fluidfrom the axial inlet of the rotating hollow device, through its(generally tubular) body, and out through the outlets located at thedistal ends of the rotating flow distributor (11). A flow of fluidmedium is thus created through the device, from the central inlet to theopenings in each rotationally peripheral end. The depicted embodiment ofthe device in FIG. 1 shows two horizontal exits and a generally T-shapedcross-section. It is, however obvious that any number of rotatingelements can be connected to a central inlet arranged in this embodimentto establish a device operating through this general principle.

FIG. 2 shows lateral and axial solid and cross-sectional views of anembodiment of the invention constructed as a tubular magneticallyactuated entity, where the principles of operational are a combinationof centrifugal force and the Bernoulli effect, as outlined for theembodiment constructed according to FIG. 1. The device in FIG. 2comprises a tubular body (21) equipped with two internal cylindricalmagnets (22), four center holes acting as inlets (23), and twoperipheral outlets provided with retaining, filters or frits (24). Solidmember(s) may be housed in both confinements (25) of the device.

FIG. 3 serves as a principle illustration of how devices embodiedaccording to the invention can be operated with two or more solidmembers in series and parallel fashion, as demonstrated with a tubulartwin chamber magnetically actuated device that is constructedessentially according to FIG. 2. By rotating the device depicted in FIG.3, fluid medium is aspirated through the four inlet holes (30) locatedon the rotational axis and diverted from there into the two confinements(31) located in each of the two rotating arms of the device, where it isforced towards the peripheral outlets (32) by the combination ofcentrifugal force and pressure differential acting on the fluid.Indirect magnetic actuation is in this example illustrated by means oftwo integrated tubular permanent magnets (33), set to interact with anexternal rotating magnetic field. In this particular embodiment, each ofthe rotating arms of the device is constructed to house two solidmembers of different functionality. Solid member A and Solid member B,both implemented as identically shaped interchangeable cartridges (34)and (35) with integrated filters/frits, that can be stacked inside thedevice. For clarity, FIG. 3 a shows the empty device, which in FIG. 3 bhas been fitted with four cartridges (34) containing Solid Member A(34), forming a reactor with a single functionality. FIG. 3 c shows thedevice operated in series interaction mode with one cartridge (34) eachcontaining Solid member A and one cartridge (35) containing Solid memberB stacked in each arm; the cartridge (34) containing Solid member Alocated close to the inlet and the cartridge (35) containing Solidmember B close to the peripheral outlets. The fluid diverted from theinlet into each chamber is first forced to percolate through cartridge(34) containing Solid Member A and directly thereafter through cartridge(35) containing Solid Member B. FIG. 3 d shows the device configured tooperate in parallel fashion, with the left arm fitted with twocartridges (34) containing Solid Member A and the right arm with twocartridges (35) containing Solid Member B. Reaction schemes requiringsequential interaction with Solid Member A followed by Solid Member Bwithout intervening liquid phase reaction (for instance direct in-linetrapping by Solid Member B of products or by-products produced in SolidMember A) will benefit from a series configuration, whereas, e.g.,schemes where further reaction(s) should take place in the fluid phasebetween the sequential treatments with Solid Members A and B willbenefit from a parallel configuration. Obviously, the number ofdifferent processing steps that can be implemented is not limited to twoas in this example; a device constructed according to FIG. 5 has, forinstance the capacity of parallel processing with four solid members,whereas dividing elements (63) and (64) of FIG. 6 can accommodate sixand three solid members in parallel, respectively, it is also obviousthat the thickness of the cartridges cart be adjusted to allow more thantwo solid member cartridges to be entrained in a serially configuredprocessing scheme, and equally obvious that the thickness of each solidmember layer can be designed at will to optimize a particular reactionscheme when several layers are implemented without being bound to acartridge format.

FIG. 4 shows an embodiment of the invention laid out as a hollowpuck-shaped device with a conventional solid magnetic spin bar (41)press-fit into two vertical grooves (42) machined in the inner wall ofthe cylinder (43), to effectively establish two separate compartmentsinside as the magnet becomes diametrically confined inside the cylinderbetween the bottom (44) of the cylindrical body and the lid (45). Foreach of the thusly formed compartments two holes (46) are drilled in theouter wall; one acting as an inlet and the other as an outlet, dependingon the rotation direction of the device. The central inlet with anintegrated frit is located axially in the bottom of the device and isobscured by the wall in FIG. 4.

Another puck-shaped embodiment is shown in FIG. 5 with an inlet hole(51) in the center of the removable lid (52) and a plurality of smalloutlet holes (53) on the sides of the body (54). Four walls (55) dividethe internal volume into four separate sectors (56). Solid membersdesigned to fit into the sectors can be easily interchanged and solidmembers of different functionality can be used in each sector forparallel processing of agent(s) transported by the fluid flow, asdescribed in detail above. The puck-shaped device has an increasedpacking aspect ratio (area perpendicular to the flow direction dividedby the packing depth) compared to the tubular device in FIG. 3, giving ahigher flow through the solid member. The relative volume of medium thatis influenced by the higher centrifugal force in the peripheral part ofthe confinement is also increased, and a larger mass of fluid willtherefore contribute to the suction forcing the fluid flow from theinlet, distributing it from the central inlet to the separateconfinements defined by the four separating walls (55) and finally tothe peripheral outlets (53). As drawn in FIG. 5, this particularembodiment is adapted for magnetic actuation by means of a permanentmagnet embedded in the bottom wall with its magnetic field lines aligneddiametrically (not shown). An alternative configuration for thisembodiment would be to attach a mechanical actuation shaft, possiblyhollow to incorporating a means for exchange of matter or energy asdescribed above, in lieu of the inlet hole (51) and instead implementingthe inlet as an identically shaped orifice located axially in the bottomwall of the device, (57) is the central axis of the flow distributor.

FIG. 6 shows yet another embodiment where the flow distributor isconstructed as a hollow puck with an interchangeable set of inserts (62,63, and 64) which are constructed with radially arranged dividingelements designed to split the rotated confinement defined by the body(65) and its lid (61) into a plurality of sectors. Each sector isconnected to an axial fluid medium inlet (hidden in the drawing by thewall of the body (65)) located in the bottom wall (66) of the device andthe peripheral fluid medium outlets are implemented as a plurality ofholes (67) drilled in the cylindrical wall of the hollow puck-Shapedbody (65). Actuation could be accomplished either by (a) magnet(s)embedded in the rotating dividing element (part 64 illustrates adividing element with provision for housing up to three embeddedmagnets) or in body of the hollow puck, or alternatively, by directmechanical coupling to a shall connected to the central axis through thelid (61).

In yet another embodiment, shown in FIG. 7, a device bearing somesimilarity to the one in FIG. 1 is laid out to operate with an enhancedcontribution from the Bernoulli principle. The fluid is drawn into thecentral inlet (71), which can optionally be designed to contain a solidmember and adapted with means for exchange of matter or energy throughthe mechanical actuator shaft (72) in the manner shown for the device inFIG. 1. After having passed through the inlet section, the fluid flow isthereafter diverted into a hollow rotating element forming two arms (72)of equal length rotating perpendicular to the axis, both arms beingsuitable for housing solid member(s) in series or in parallel,configurations explained in FIG. 3. The distal end of each rotating armis connected to a short venturi tube (74), constructed per se accordingto principles that are well known in prior art. This pair of venturitubes is mounted in opposite direction, perpendicular to the peripheralexit (75) of each arm, and with their through paths axes aligned withthe plane described by the circular motion of the arms (73). Whenactuated as indicated by the arrow in FIG. 7, the rotation causes fluidto flow through the venturi tubes (74), whereby the faster moving liquidpassing the outlets (75) will cause a decrease in pressure, according tothe Bernoulli principle. The pressure differential between the centralinlet (which much less affected by the Bernoulli effect) and theperipheral exits connected to the venturi tubes causes fluid to flowfrom the inlet to the outlets. The device is mechanically actuated by ahollow shaft (72), the lumen of which is well suited to act as a conduitfor transfer of thermal energy, electromagnetic radiation, or foraddition of chemical agents and product/by-product removal.

FIG. 8 shows an exploded view of a four part device of the invention,embodied by an internal element (81) that rotates clockwise, with allother parts kept static. Rotating the internal element (81) as indicatedby the arrow in FIG. 8 creates a flow into the static element (82),where a plurality of peripheral outlets (83) are located. Solidmember(s) can be included in several confinements in the drawn example;integrated with the central inlet (84), in the internal rotating element(80), and/or in the flow channels (85) of the static element (82). Thedevice is covered by a lid (86) joined with the static element (82), thelid having a passageway for allowing a mechanical shaft (87) to actuatethe internal rotating element (81), the actuator shaft optionally beinghollow and equipped with a means for exchange of matter or energy. Adevice constructed according to this principle has the advantage ofestablishing a strong flow without causing a rotational vortex in thebulk fluid medium.

In yet another embodiment of the device, illustrated in FIG. 9, one ormore of the flow channel(s) of the flow distributor is/are laid out withpart of its/their peripheral paths aligned with, and positioned closeto, the circumference of the rotation plane described by the device whenit is pivoting around its axis; the orientation of the section(s) of theflow path(s) hence deviate(s) significantly from the predominantlyradial direction devised in the embodiments shown in figures referred tohitherto. A flow distributor with its flow channel(s) laid out in thisway is preferentially combined with a flow-operated check valve(designed per se according to principles well known in prior art)located in the central fluid medium inlet, which is designed to allowthe fluid medium to flow freely in through this inlet, but blocks itfrom exiting there. The peripheral exit(s) can be left open. When laidout according to these criteria, the device is designed to operatemainly according to the principle of inertia, where either alterationsup and down in the angular speed of a continuous rotation pattern, oralternatively rocking the device back and forth by an oscillatingrotational movement that integrates to zero net rotation over time, willresult in fluid flowing through the confinements of the flowdistributor, mediated by the inertial action of the angularacceleration/deceleration on the fluid in the peripheral section(s) ofthe flow channel(s) that is(are) aligned with the direction of rotation.Thus, in the device variant shown in FIG. 9, the flow distributor has apuck-shaped body (90) with an inlet (91) at the bottom, positionedcentrally with respect to the rotational axis. This inlet comprises asmall cylindrical compartment that retains a loosely fit elastomericdisc (97) which has a flat bottom and a pattern of radially orientedridges on the upper surface in order to form an integrated check valve,the principle of which is well known per se in prior art. The flatbottom surface of the valve membrane will block fluid from flowing outof the device through the inlet, whereas the radial pattern of ridges onthe upper surface of the membrane allows fluid that flows past theloosely lit membrane to enter into the device. The valve hence allowsthe fluidic medium to be drawn into the confinement (92) that is adaptedto accommodate (a) solid member(s), which (if necessary) is/are kept inplace by a suitable mesh or frit (93). The solid member confinement (92)is oriented radially relative to the rotation axis, which isperpendicular to the centrum point of the drawing plane in section A-Aof FIG. 9. The confinement (92) is in turn connected to the inertialchannels (94), which are oriented along with the circumference of thepuck-shaped body (90) close to its cylindrical wall. This circularorientation ascertains that inertial force will act on the fluidicmedium in the inertial channels (94) to cause a complete pumping actionfrom the inlet (91) to the outlet(s) (95) whenever the angular velocityof the device goes through an acceleration/deceleration cycle, but notwhen it is rotating at a steady rate. The angularacceleration/deceleration required to establish the inertial pumping canbe created either by rocking the device back and forth without a netrotation over time, or by alternations up and down in the angularvelocity of a continuous rotation. A particular advantage of thisembodiment is that the internal flow through the flow distributor andits agitation of the bulk fluidic medium can be individually tunedwithout giving rise to vortex formation.

It is realized, that the fluidic flow through a device with twoperipherally located outlets as disclosed in FIG. 9 will be underinfluence of both inertial, centrifugal, and Bernoulli forces. Analternative arrangement of the outlet channels, to form a device thatoperates almost solely on the basis of inertia, is shown in FIG. 10,which has the added benefit of having the fluid flow outlet locatedcentrally to the device. In this embodiment, which can be described asan alternative outlet variant of the device shown in FIG. 9, the fluidflow is not allowed to escape the flow distributor through a pair ofperipherally located outlets (95) as in the device shown in FIG. 9, butinstead guided from the inertial channels (104) towards a single outlet(105) that is positioned on the rotational axis. This is accomplished bymeans of an internal pair of short vertical channels (108) which lead toa separate diametrically oriented channel (109) located on top of theconfinement (102) and the inertial channels (104). Also shown are thepuck-shaped body (100), a mesh or frit (103), and valve (107) similar tothe valve (97) in FIG. 9, described above. The fluid flow established bythe angular momentum acting on the fluid in the inertial channels (104)is thereby channeled back towards the rotational axis of the device(against the centrifugal force) and routed to exit through a singleoutlet (105) which is designed to fit exactly into the central inlet(101) of the device. This configuration not only has the obviousadvantage of allowing several devices to be stacked for operation inseries; it also has an additional advantage in that the internal fluidflow will be governed practically only by inertial forces, since i) thecentrifugal force is nullified by rerouting the fluid back to therotational axis; and ii) the Bernoulli effect is negligible since boththe inlet and outlet are situated on the rotational axis. Hence, byapplying a sequence of angular accelerations and decelerations in astepwise fashion, the fluid flow can be rapidly altered. It is thuspossible to carry out stopped flow reactions in a single solid member,or stepped transfer between two or more solid members connected inseries by stacking. Although the device examples shown in FIGS. 9 and 10are both equipped with magnets (96 and 106, respectively) for(electro)magnetically coupled actuation, it is obvious that theprinciple can be implemented equally elegant by mechanical couplingthrough a shaft, preferentially attached to and integrated with thecentral inlet, in which case the shall can also provide a means forexchange of matter and energy with the enclosed solid member.Alternatively, if a device constructed according to FIG. 10 is combinedwith mechanical coupling through a hollow actuator shaft through thecentral outlet, the fluid being pumped out of the reactor can beconveyed from the reaction vessel by means of the actuator shaft.

A device operating mainly according to the principles of inertia canalso be realized by routing the internal flow channel as a single ormultiple parallel archimedean spiral(s), as embodied in FIG. 11 wherefour archimedean spirals (113) have been laid out in parallel. In thisconfiguration the spirally shaped channels combine the functions of aconfinement for housing solid member(s), and that of inertial channel(s)(since the archimedean spirals are oriented largely as stipulated forthe inertial segments of the internal channeling in the embodiment shownin FIG. 9). Due to the advantageous surface-to-volume of the spirallyarranged channels, this embodiment is particularly useful when solidmembers are to be implemented as a coating on the flow distributorsurface. The principle of operation is very similar to the embodimentshown in FIG. 9 and needs no further explanation; the main difference isthat the device of FIG. 11 lacks a separate compartment for housingsolid member(s). Instead, the archimedean spirals double as compartmentsand inertial channels. Also shown are puck-shaped body (110), thecentral inlet (111) of the device, valve (112) similar to the valve (97)and (107) described above, peripheral outlets (114), and magnets (115).

The final embodiment disclosed is shown in FIG. 12 and represents avariant of the inertial device based on archimedean spirals of FIG. 11,where the outlet of the archimedean spirals (126) is routed back to thecentral outlet (124). The principle and advantages of this outletrouting variant was discussed for the device disclosed in FIG. 10 above,and need not be repeated here. Also shown are the puck-shaped body(120), the central inlet (121) of the device, valve (122) similar to thevalve (97) and (107) described above, four archimedean spirals (123),and magnets (125).

The means for by rotating, rocking, wagging, or oscillating of a deviceaccording to the invention can be the actuator shaft (14) (FIG. 1), (72)(FIG. 7), and (87)(FIG. 8); or a magnet (22)(FIG. 2); (33)(FIG. 3),(41)9 FIG. 4), (96)(FIG. 9), (115)(FIG. 10), (115)(FIG. 11), and (120(FIG. 12), the magnet being contained in the device driven by afluctuating external magnetic field, said fluctuating field, beingestablished either by properly positioning in the vicinity of the devicea ferromagnetic or electromagnetic field source actuated by mechanicalmeans, or a plurality of stationary electromagnets that are actuated byan electronic circuit in the proper sequence required for thatparticular agitation mode.

As to a further discussion of the manner of usage and operation of thepresent invention, the same should be apparent from the abovedescription. Accordingly, no further discussion relating to the mannerof usage and operation will be provided.

With respect to the above description then, u is to be realized that theoptimum dimensional relationships for the parts of the invention, toinclude variations in size, materials, shape, form, function, and mannerof operation, assembly and use, are deemed readily apparent and obviousto one skilled in the art.

Therefore, the foregoing is considered as illustrative only of theprinciples of the invention. Further, since numerous modifications andchanges will readily occur to those skilled in the art, it is notdesired to limit the invention to the exact construction and operationshown and described, and accordingly, all suitable modifications andequivalents may be resorted to, falling within the scope of theinvention.

Example 1

Three identical cylindrical devices were prepared essentially according,to FIG. 2 from 46 mm long pieces of poly(tetra fluoroethylene) (PTFE)tubing with inner and outer diameters of 6.3 and 6.5 mm, respectively. A2 mm diameter drill was used to prepare two pairs of holes perpendicularto each other in the middle of each tube, where after two annular rareearth permanent magnets were inserted from each end and press-lit intothe tubes as far as possible without obstructing the central inletholes. Punched pieces of polymeric, mesh filters were inserted in bothends, following bylining each arm with ˜500 mg of Dowex Monosphere 550ALC NG strong anion exchange resin in the hydroxide ion form, and theperipheral ends were furnished with polymeric mesh filters to keep theion exchange resin in place. The three devices were thereafter placed inseparate E-flasks, each containing 100 ml of a prepared solutioncontaining 1 liter of water, 10 mg of bromophenol blue as pH indicator,1 g sodium chloride, and 0.08 ml of 37% (w/w) hydrochloric acid. Two ofthe devices were rotated magnetically at 300 rpm (Experiments 1.1 and1.2) whereas the third was left unrotated (Experiment 1.3). The deviceused in Experiment 1.2 had its inlet holes blocked by tape, so no liquidcould enter or leave there. The inlet holes were left unobstructed inExperiments 1.1 and 1.3. The efficiency of the mass transfer between thesolution and the ion exchanger resin inside the devices liquid wasestimated by the time until the indicator visibly turned blue. Theoutcome of the experiment is accounted for in Table 1.

TABLE 1 Mass transfer efficiency enhancement by rotating a tubularreactor device. Time until color Experiment Rotation (rpm) Central Holechange (s) 1.1 300 Open 20 1.2 300 Sealed 300 1.3 Unagitated Open 900

In the present set-up, the simple neutralization of hydrochloric acid byhydroxide ions bound as counter-ions to an anion exchanger serves as anexample reaction. The requirements for the reaction to take place areeither that the hydronium ions that are part of the acidic test mediumare transported to the ion exchanger within the device, where they reactwith the hydroxide ions that are attached as counter-ions; or thatchloride ions from the sodium chloride added in the solution aretransported to the solid reagent contained within the device where theyare exchanged for hydroxide ions attached to the ion exchanger ascounter-tons. These must in turn be transported back to the solution toreact with the hydronium ion excess in the acidic bulk medium. Common toboth these reactions is that they require that the reactant betransported to the ion exchanger (the solid member) by means of thefluidic test medium, which in this case is based on water. This set-uphence serves as a simple but highly illustrative demonstration of theenhanced mass transfer that is established through the device byrotation, and unequivocally shows that rotation of the device resultedin a mass transfer that was at least 45 times more efficient compared toan unstirred identical device in the same reaction vessel. Experiment10.3 further verifies that less than 7% of this mass transferenhancement can be explained b turbulent convective transport throughthe meshes located at the peripheral exits. A mass transfer enhancementincrease this significant shown by the rotated device with its centralholes unobstructed can only be explained by the establishment of afluidic flow through the device accomplished by the combination of itsdesign and its rotation. It hence serves as a demonstrator of thegeneral principle of establishing a transfer of fluid between the insideof the device (medium, solid, etc) and the fluidic medium in which it isrotated.

Example 2

A device prepared essentially according to the device described in FIG.9 was filled with 0.75 g ion exchanger, Dowex Monosphere A550 LCNG OHand immersed in a solution of 3 mL hydrochloric acid (0.16 M) withdissolved phenolphthalein, 0.33 g NaCl, diluted up to 250 mL with MilliQwater. A 12VDC wiper motor was connected and an oscillation motion wasperformed at 55 sweep/min. The reaction was completed after 16 minutesas indicated by the change of color of the indicator.

As a control experiment the device was used under the same conditionsbut without applying the oscillating motion where no reaction occurredfor more than 1 hour.

1. A device for performing biological or chemical transformation, orphysical or chemical trapping in fluidic media comprising: a. a hollowtubular flow distributor having at least one central fluid medium inlet,at least one peripheral fluid medium outlet, and at least oneconfinement wherein said transformation or trapping is performed; and b.a means for rotating, rocking, wagging, or oscillating the device. 2.The device according to claim 1, wherein the confinements of the flowdistributor houses one or more solid members that participate in orfacilitate(s) a biological or chemical transformation involving at leastone agent distributed with the flow, or causes said agent to becomephysically or chemically trapped by a solid member.
 3. The deviceaccording to claim 2, wherein each solid member is provided in one ormore cartridges or as monolithic packing, which are placed within the atleast one confinement.
 4. The device according to claim 3, wherein saidcartridges are replaceable.
 5. (canceled)
 6. (canceled)
 7. (canceled) 8.(canceled)
 9. The device according to claim 1, wherein the flowdistributor is made from or coated with a material that is able tocatalyze at least one an agent to undergo a chemical reaction. 10.(canceled)
 11. The device according to claim 1, wherein the means forrotating, rocking, wagging, or oscillating the device is an elementproducing a magnetic fields.
 12. The device according to claim 1,wherein the means for rotating, rocking, wagging, or oscillating thedevice is a solid or hollow shaft mechanically connected to an externalactuating device.
 13. The device according to claim 1, wherein theconfinement contains a solid member selected from the group consistingof: a. a catalyst; b. a solid phase containing a physically trapped orchemically bonded reagent capable of entering a chemical reaction withan agent transported by the fluidic flow; c. an immobilized biologicalentity capable of transforming agents supplied by the fluidic flow; d. asupport material suitable for carrying out solid phase synthesis; e. asolid sorbent capable of trapping matter from the fluidic flow; and f. astationary phase suitable for chromatographic separation.
 14. (canceled)15. A method of performing biological or chemical transformation, orphysical or chemical trapping in fluidic media comprising: c. providingthe device of claim 1; and d. creating a convective flow of fluidicmedium through the device by rotating, rocking, wagging, or oscillatingthe device.
 16. The device according to claim 1, wherein the flowdistributor is coated with a material that is capable of chemicallytransforming at least one agent introduced to the flow channel.
 17. Thedevice according to claim 2, wherein two or more confinements areconnected in series, and are filled with different solid members capableof carrying out different chemical transformation.
 18. The deviceaccording to claim 2, wherein two or more confinements are connected inparallel and are filled with different solid members capable of carryingout different chemical transformation.
 19. The device according to anyof claim 18, comprising a combination of confinements connected inseries and parallel.